{"doi":"10.1210/mend.11.3.9894","title":"Thapsigargin-Induced Gene Expression in Nonexcitable Cells Is Dependent on Calcium Influx","abstract":null,"journal":"Molecular Endocrinology","year":1997,"id":591866,"datarank":1.5904983338215384,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":1.0571961245981263,"self_endowment_contribution":0.5333022092234121,"citer_contribution":1.0571961245981263,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":22,"citers_with_citation_signal":21,"citers_with_endowment":21,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":654117,"name":"Robert P. Wersto","orcid":null,"position":1,"is_corresponding":false},{"id":1514408,"name":"Susan Hobson","orcid":null,"position":2,"is_corresponding":false},{"id":230686,"name":"Elise C. Kohn","orcid":"0000-0002-8631-9762","position":3,"is_corresponding":false},{"id":51828,"name":"Karin D. Rodland","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Thapsigargin-Induced Gene Expression in Nonexcitable Cells Is Dependent on Calcium Influx","abstract":"Agents such as thapsigargin and endothelin elevate intracellular calcium levels by a combination of calcium release from intracellular stores and calcium influx across the plasma membrane; however, the relative contribution of influx vs. release in modulating calcium-dependent gene expression is not as well understood in nonexcitable cells as in excitable cells. In this report we have been able to separate thapsigargin-induced elevation of intracellular calcium into release and influx components, using carboxyamido-triazole (CAI), a known inhibitor of calcium influx with antiproliferative activity against a number of human carcinomas, to selectively inhibit influx without affecting release. The results of these experiments indicate that the ability of thapsigargin to induce calcium-dependent gene expression in nonexcitable cells is dependent on the induction of calcium influx, presumably through store-operated calcium channels. CAI treatment specifically inhibited thapsigargin- or endothelin-stimulated expression from the c-fos promoter in Rat-1 cells and in epithelial cell lines derived from ovary and breast. Use of the VL30 model system confirmed the ability of CAI to inhibit calcium-dependent gene expression and further demonstrated that the ability of elevated calcium to synergize with other signaling pathways required close temporal coupling. In addition to inhibiting endothelin-induced calcium influx, CAI treatment also resulted in a partial inhibition of IP3 production and calcium release. CAI treatment also blocked the increase in ERK1 kinase activity observed in response to either endothelin or thapsigargin, suggesting a role for calcium influx in the activation of mitogen-activated protein kinase pathways.","is_dataset_classified":null,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9058375","pmcid":null,"openalex_id":"https://openalex.org/W2123238323","authors":[],"funders":[],"total_grants":0,"fwci":1.4618,"citation_percentile":0.82702403,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2016,"count":1},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2023,"count":1},{"year":2024,"count":2}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://press.endocrine.org/doi/full/10.1210/mend.11.3.9894","host_type":"publisher"},{"url":"https://doi.org/10.1210/mend.11.3.9894","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9058375","host_type":"repository"}],"fields_of_study":["Signaling Pathways in Disease","Protein Kinase Regulation and GTPase Signaling","Cell death mechanisms and regulation"],"mesh_terms":["Animals","Calcium","Calcium Channel Blockers","Cell Line","Enzyme Activation","Gene Expression Regulation","Imidazoles","Triazoles","Chloramphenicol O-Acetyltransferase","Genes, fos","Calcium-Calmodulin-Dependent Protein Kinases","Genes, Reporter","Thapsigargin","Endothelin-1","Rats"],"keywords":["Thapsigargin","Calcium","Biology","Calcium in biology","Cell biology","Endocrinology","Endothelin 1","Voltage-dependent calcium channel","Calcium channel","T-type calcium channel","Internal medicine","Intracellular","Biochemistry","Receptor","Medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T11:03:45.813327Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}